Rejected

Temporomandibular joint disorder is a prevalent orofacial pain condition involving sensitization and activation of trigeminal nociceptive neurons. Dietary supplementation with a proanthocyanin-enriched grape seed extract (GSE) was found to inhibit trigeminal nociception in a chronic TMD model. In this study, the cellular mechanisms by which GSE inhibits sustained trigeminal nociception in male and female Sprague Dawley rats were investigated. Some animals were supplemented with 0.5% GSE dissolved in their water one week prior to neck muscle inflammation induced by injection of complete Freund's adjuvant into the trapezius. To investigate the mechanism of GSE, some animals were injected intracisternally with antagonists of 5-HT3, 5-HT7, GABAA, or GABAB, receptor prior to jaw opening. In males and females, trapezius inflammation prior to jaw opening resulted in sustained mechanical hypersensitivity of trigeminal nociceptors that was significantly inhibited by GSE. Further, GSE beginning 14 days post jaw opening also inhibited trigeminal nociception. Intracisternal injection of antagonists of the 5-HT3/7 and GABAB, but not GABAA receptors reduced the anti-nocifensive effect of GSE in both sexes. Neuronal expression of GABAB protein and mRNA in the spinal cord and trigeminal ganglion were detected. The inhibitory effect of GSE is mediated via activation of 5-HT3/7 receptors and GABAB to enhance central descending inhibitory pain pathways and suppress ongoing trigeminal nociception. Further, our findings support the use of GSE as a dietary supplement in the management of pain associated with TMD and other orofacial pain conditions involving central sensitization and dysfunction of descending pain modulation.

Our previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

The novel coronavirus disease-2019 (COVID-19) pandemic that started in December 2019 has affected over 95 million people and killed over 2 million people as of January 19, 2021. While more studies are published to help us understand the virus, there is a dearth of studies on the clinical characteristics and associated outcomes of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on the African continent.

Posterior cruciate ligament (PCL) injuries often occur as part of a multiligament injury pattern and can present a significant challenge to the treating surgeon. When PCL reconstruction is indicated, complications can arise in the intraoperative and postoperative period that lead to poor outcomes. These complications include neurovascular injury, fracture, compartment syndrome, persistent posterior laxity, motion loss, residual knee pain, osteonecrosis, and heterotopic ossification. The purpose of this review is to highlight complications associated with PCL reconstruction and strategies to avoid them.

The advent and availability of COVID-19 vaccines has led patients to pose a number of questions to their headache healthcare providers. In retrospect, it is perhaps surprising that these questions did not come earlier-for example around annual flu shot campaigns. However, COVID-19 has brought into focus questions about whether vaccines have an impact on the management of migraine and other headache disorders.

Pruritus is known to be a common complication in hepatitis patients, but the exact frequency and degree are not fully elucidated. Thus, we evaluated pruritus of 450 patients with chronic liver disease at our hospital. Pruritus was observed in 240 (53%) of the patients. Pruritus was significantly associated with males (OR = 1.51, P = 0.038) and patients with alkaline phosphatase (ALP) ≥ 200 U/L (OR = 1.56, P = 0.0495) and was significantly less in HBsAg-positive patients (OR = 0.449, P = 0.004). Seasonally, there was no difference in the frequency of pruritus between summer and winter. Of the 24 refractory pruritus patients treated with nalfurafine, 17 (71%) indicated improvement of itch, which is defined as a decrease in the visual analog scale score ≥ 30 mm. Pruritus was improved by nalfurafine both during daytime and nighttime in the Kawashima's scores evaluation. All patients who received nalfurafine exhibited improved Kawashima's scores ≥ 1 point during the daytime or nighttime. In conclusion, pruritus occurred in > 50% of patients with chronic liver disease, and predictors of pruritus were males and ALP ≥ 200 U/L. Nalfurafine may be useful for pruritus, regardless of whether daytime or nighttime.

To provide an overview on the status of clinical research in neurology in Germany.

The importance of circadian rhythm dysfunctions in the pathophysiology of neurological diseases has been highlighted recently. Chronopharmacology principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients could optimize therapeutic management. According to these principles, chronopharmacology takes into account: the individual differences in patients' clocks, the rhythmic changes in the organism sensitivity to therapeutic and side effects of drugs, and the predictable time variations of disease. This review examines the current literature on chronopharmacology of neurological diseases focusing its scope on epilepsy, Alzheimer and Parkinson diseases, and neuropathic pain, even if other neurological diseases could have been analyzed. While the results of the studies discussed in this review point to a potential therapeutic benefit of chronopharmacology in neurological diseases, the field is still in its infancy. Studies including a sufficiently large number of patients and measuring gold standard markers of the circadian rhythmicity are still needed to evaluate the beneficial effect of administration times over the 24-h day but also of clock modulating drugs.